NAD +
D- Alanine
1. Glyoxylate Cycle Metabolism 2. Citric Acid Cycle
Acetyl-CoA
Acetyl-CoA is an "activated" two carbon compound found in many central metabolic pathways, including the citric acid cycle, the glyoxylate cycle, fatty acid synthesis, fatty acid oxidation, isoprene metabolism, amino sugar
metabolism, ketone body metabolism, and cholesterol biosynthesis. The term "activated" used to describe the compound comes partly from the nature of the high energy thioester bond in the molecule with a of -31.5 kJ/mol.
Acetyl-CoA is one of the most ubiquitous metabolites in biological systems.
Acetyl-CoA is also an allosteric regulator of the enzymes pyruvate kinase (turns it off), pyruvate carboxylase (turns it on).
See also: Coenzyme A, Citric Acid Cycle, Pyruvate Kinase, Pyruvate Carboxylase
INTERNET LINKS:
1. Glyoxylate Cycle Metabolism
Coenzyme A (CoA or CoASH)
Coenzyme A (A for acyl) participates in activation of acyl groups in general, including the acetyl group derived from pyruvate. The coenzyme is derived metabolically from ATP, the vitamin pantothenic acid, and -mercaptoethylamine (Figure 18.26). A free thiol on the last moiety is the functionally significant part of the coenzyme molecule; the rest of the molecule provides enzyme binding sites. In acylated derivatives, such as acetyl-coenzyme A, the acyl group is linked to the thiol group to form an energy-rich thioester. The acylated forms of coenzyme A will be designated here as acyl-CoA, and the unacylated form as CoA-SH.
The energy-rich nature of thioesters, as compared with ordinary esters, is related primarily to resonance stabilization (Figure 14.9). Most esters can resonate between two forms (Figure 14.9). Stabilization involves Pi-electron overlap, giving partial double-bond character to the C-O link. In thioesters, the larger atomic size of S (as compared with O) reduces the Pi-electron overlap between C and S, so that the C-S structure does not contribute significantly to resonance stabilization. Thus, the thioester is destabilized relative to an ester, so that its G of hydrolysis is increased.
The lack of double-bond character in the C-S bond of acyl-CoAs makes this bond weaker than the corresponding C-O bond in ordinary esters, in turn making the thioalkoxide ion (R-S-) a good leaving group in nucleophilic displacement reactions. Thus, the acyl group is readily transferred to other metabolites, as occurs, in fact, in the first reaction of the citric acid cycle.
Common metabolic reactions involving Coenzyme A are shown below.
1. Acetate + CoASH + ATP <=> Acetyl-CoA + AMP + PPi (catalyzed by Acetate Thiokinase).
2. Pyruvate + NAD+ + CoASH <=> Acetyl-CoA + NADH + CO2 (catalyzed by Pyruvate
Dehydrogenase).
3. 3-Ketoacyl-CoA + CoASH <=> Acyl-CoA (less 2 carbons) + Acetyl-CoA (catalyzed by Thiolase).
4. Malonyl-CoA + ACP <=> Malonyl-ACP + CoASH (catalyzed by Malonyl-CoA-ACP Transacylase)
5. Acetyl-CoA + ACP <=> Acetyl-ACP + CoASH (catalyzed by Acetyl-CoA-ACP Transacylase) 6. Acyl-CoA + Carnitine <=> Acyl-Carnitine + CoASH (catalyzed by Carnitine Acyltransferase I) 7. Acyl-Carnitine + CoASH <=> Acyl-CoA + Carnitine (catalyzed by Carnitine Acyltransferase II)
See also: Pyrimidine Catabolism
Pantothenic Acid
Pantothenic acid is a vitamin that forms an essential part of the acyl-carrier
moiety, coenzyme A.
See also: Coenzyme A
-Mercaptoethylamine
-Mercaptoethylamine is a structural part of coenzyme A to which the acyl groups are attached (see coenzyme A).
See also: Acyl Groups
Acyl Groups
Acyl groups refer to carbon chains derived from fatty acids or simple organic acids, such as acetic acid. Examples of fatty acid groups are shown in Table 10.1. Coenzyme A is a common carrier of acyl groups in cells. Fats, some proteins, glycolipids, and sphingolipids may all contain one or more acyl groups.
See also: Coenzyme A, Fatty Acids
Fatty Acids
Fatty acids in the body arise either from biosynthesis from acetyl-CoA or from breakdown of fats and phospholipids. Free fatty acids are rarely found in the body. Fatty acids are transported in the blood complexed to serum albumin. Fatty acids can be saturated (no double bonds) or unsaturated (contain double bonds). Unsaturated fatty acids of biological origin predominantly contain cis double bonds.
Mammals are unable to synthesize some fatty acids, making these fatty acids essential components of their diet.
Common saturated fatty acids include palmitic acid and stearic acid. Common unsaturated fatty acids include oleic acid, palmitoleic acid, linoleic acid, linolenic acid. The fatty acid, arachidonic acid, is a precursor of the prostaglandins.
See also: Acetyl-CoA, Fats, Albumin, Fatty Acid Activation, Oxidation of Saturated Fatty Acids, Oxidation of Unsaturated Fatty Acids, Fatty Acid Biosynthesis Strategy, Palmitate Synthesis from Acetyl-CoA, Fatty Acid Desaturation, Essential Fatty Acids, Control of Fatty Acid Synthesis, Molecular Structures and Properties of Lipids (from Chapter 10)
Palmitic Acid (Palmitate, n-Hexadecanoic Acid)
Palmitic acid is a 16-carbon saturated fatty acid that is the end product of synthesis of the fatty acid synthase complex. Palmitic acid (as palmitoyl-CoA) is a starting substrate for synthesis of both longer chain fatty acids and unsaturated fatty acids.
Palmitic acid (in the form of palimitoyl-CoA) is also a precursor of the sphingolipids (Figure 19.12).
See also: Fatty Acids, Table 10.1, Synthesis of Long Chain Fatty Acids, Fatty Acid Desaturation, Fatty Acid Synthase, Palmitate Synthesis from Acetyl-CoA
Palmitoyl-CoA
Palmitoyl-CoA is the product of synthesis catalyzed by the fatty acid synthase complex. Cleavage of the thioester bond of the CoA group yields palmitic acid. Palmitoyl-CoA is also a precursor of the sphingolipids (see here)
See also: Fatty Acids, Table 10.1, Synthesis of Long Chain Fatty Acids, Fatty Acid Desaturation, Palmitate Synthesis from Acetyl-CoA, Biosynthesis of Sphingolipids, 3-Ketosphinganine
INTERNET LINKS:
1. Sphingolipid Metabolism